Isoflurane Attenuates Blood–Brain Barrier Disruption in Ipsilateral Hemisphere After Subarachnoid Hemorrhage in Mice
Background and Purpose—We examined effects of isoflurane, volatile anesthetics, on blood–brain barrier disruption in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice.
Methods—Animals were assigned to sham-operated, SAH+vehicle–air, SAH+1%, or 2% isoflurane groups. Neurobehavioral function, brain water content, Evans blue dye extravasation, and Western blotting for sphingosine kinases, occludin, claudin-5, junctional adhesion molecule, and vascular endothelial cadherin were evaluated at 24 hours post-SAH. Effects of sphingosine kinase (N,N-dimethylsphingosine) or sphingosine-1-phosphate receptor-1/3 (S1P1/3) inhibitors (VPC23019) on isoflurane’s action were also examined.
Results—SAH aggravated neurological scores, brain edema, and blood–brain barrier permeability, which were prevented by 2% but not 1% isoflurane posttreatment. Two percent isoflurane increased sphingosine kinase-1 expression and prevented a post-SAH decrease in expressions of the blood–brain barrier-related proteins. Both N,N-dimethylsphingosine and VPC23019 abolished the beneficial effects of isoflurane.
Conclusions—Two percent isoflurane can suppress post-SAH blood–brain barrier disruption, which may be mediated by sphingosine kinase 1 expression and sphingosine-1-phosphate receptor-1/3 activation.
- blood–brain barrier
- early brain injury
- sphingosine kinase-1
- sphingosine-1-phosphate receptor
- subarachnoid hemorrhage
- Received April 19, 2012.
- Revision received May 14, 2012.
- Accepted May 17, 2012.
- © 2012 American Heart Association, Inc.